Two different mechanisms have been proposed by which dopamine and dobutamine cause negative interferences for tests that use peroxidase- catalyzed oxidation of hydrogen peroxide to generate chromophores. We reinvestigated these interferences by testing structurally related compounds (dopamine, dobutamine, L-dopa, L-methyldopa, and tyramine) with a wide range of analyte and drug concentrations for four different peroxidase-generated chromophore-based tests: uric acid (UA), creatinine (Cre), total cholesterol (TC), and glycerol-blanked triglycerides (TG). Dopamine, dobutamine, L-dopa, and L-methyldopa caused dose-dependent decreases on the four tests. The results were analyzed as log molar analyte/drug (A/D) ratios. With a maximal inhibition of about 75 percent, two sigmoidal curves were obtained: one for UA and Cre, the other for TC and TG. Little if any inhibition occurred at a (Cre),(UA)/D ratio of greater than 30 to 40; and at a (TC), (TG)/D ratio of 60 to 70. The inhibition was log-linear when the (Cre),(UA)/D ratio was 1 to 10 and (TC), (TG)/D ratio was 2 to 20. While the 50 percent inhibition by the four drugs was close to equimolar for UA and Cre, a 3 to 4-fold excess of analyte over the drug was required for inhibition of TC and TG at this level. The results show that, in contrast to earlier suggestions, all four drugs share the inhibitory mechanism. The observed differences between the two groups of analytes (UA and Cre vs. TC and TG) are apparently related to the use of different chromogens (monitoring at 546 vs. 505 nm). Additional studies are in progress to elucidate the precise mechanism of drug inhibition with peroxidase-catalyzed reaction(s) and to identify any modifications that would minimize or eliminate the interference.